Despite significant advances in the treatment of asthma, optimal clinical therapy for patients with this increasingly common and potentially debilitating disease is still in flux. The first trial we propose for the Asthma Clinical Research Network (ACRN) emerges from expert-based guidelines recommending that individuals with mild-moderate persistent asthma symptoms, who comprise about 50% of patients requiring chronic asthma therapy, should be treated with controller agents such as inhaled corticosteroids (ICS). However, this may lead to over-treatment of many individuals who do not require such therapy. Data from a completed ACRN trial suggest that more than 60% of patients whose symptoms were controlled with continuous ICS did not experience exacerbations when discontinuing this medication. Our retrospective analysis of this trial suggests that changes in sputum eosinophils may identify 80% of the patients who can successfully discontinue inhaled corticosteroids. If confirmed, such a tool could prevent unnecessary treatment for a large cohort of asthmatics and result in an estimated $2 billion of savings per year. It could also identify patients requiring further therapy. We propose a double blind, placebo-controlled study to test this hypothesis. Our second trial focuses on patients with more severe disease, who account for a disproportionate amount of asthma-related morbidity. For patients whose symptoms persist in spite of treatment with ICS and a long-acting -agonist, alternatives are needed to the current recommendation of treatment with higher doses of ICS. Newer agents, such as leukotriene modifiers, may be beneficial for such patients. We will examine the effect of adding a leukotriene modifier to ICS and a long-acting -agonist vs. increasing the dosage of ICS with continuation of a long-acting -agonist among patients with moderate to severe asthma. Both trials will use asthma deteriorations as the primary outcome. In the second trial, we will also examine if the response to ICS therapy is associated with haplotypic variations in the gene coding for the glucocorticoid receptor and if the response to leukotriene modifiers is associated with polymorphisms of the LTC4 synthase promoter. This latter analysis may permit us to individualize therapy and therefore maximize benefit, decrease toxicity, and decrease cost.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Cooperative Clinical Research--Cooperative Agreements (U10)
Project #
5U10HL074227-04
Application #
7116386
Study Section
Special Emphasis Panel (ZHL1-CSR-B (M1))
Program Officer
Smith, Robert A
Project Start
2003-09-15
Project End
2008-07-31
Budget Start
2006-08-01
Budget End
2007-07-31
Support Year
4
Fiscal Year
2006
Total Cost
$1,004,402
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115
Lugogo, Njira; Green, Cynthia L; Agada, Noah et al. (2018) Obesity's effect on asthma extends to diagnostic criteria. J Allergy Clin Immunol 141:1096-1104
Nyenhuis, Sharmilee M; Krishnan, Jerry A; Berry, Alalia et al. (2017) Race is associated with differences in airway inflammation in patients with asthma. J Allergy Clin Immunol 140:257-265.e11
Dunn, Ryan M; Lehman, Erik; Chinchilli, Vernon M et al. (2015) Impact of Age and Sex on Response to Asthma Therapy. Am J Respir Crit Care Med 192:551-8
Peters, Stephen P; Bleecker, Eugene R; Kunselman, Susan J et al. (2013) Predictors of response to tiotropium versus salmeterol in asthmatic adults. J Allergy Clin Immunol 132:1068-1074.e1
Bonini, Matteo; Permaul, Perdita; Kulkarni, Tejaswini et al. (2013) Loss of salmeterol bronchoprotection against exercise in relation to ADRB2 Arg16Gly polymorphism and exhaled nitric oxide. Am J Respir Crit Care Med 188:1407-12
Calhoun, William J; Ameredes, Bill T; King, Tonya S et al. (2012) Comparison of physician-, biomarker-, and symptom-based strategies for adjustment of inhaled corticosteroid therapy in adults with asthma: the BASALT randomized controlled trial. JAMA 308:987-97
Sutherland, E Rand; Goleva, Elena; King, Tonya S et al. (2012) Cluster analysis of obesity and asthma phenotypes. PLoS One 7:e36631
McGrath, Kelly Wong; Icitovic, Nikolina; Boushey, Homer A et al. (2012) A large subgroup of mild-to-moderate asthma is persistently noneosinophilic. Am J Respir Crit Care Med 185:612-9
Szefler, Stanley J; Chinchilli, Vernon M; Israel, Elliot et al. (2012) Key observations from the NHLBI Asthma Clinical Research Network. Thorax 67:450-5
Wechsler, Michael E; Castro, Mario; Lehman, Erik et al. (2011) Impact of race on asthma treatment failures in the asthma clinical research network. Am J Respir Crit Care Med 184:1247-53

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